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1.
Genes Dev ; 37(5-6): 191-203, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859340

RESUMO

Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C's protein abundance, distribution, or ability to traffic other mRNAs. Conversely, Kif1c mRNA localization to protrusions is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mislocalization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein-protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle that impacts the functions of proteins encoded by protrusion-enriched mRNAs in nonneuronal cells.


Assuntos
Cinesinas , Proteínas , RNA Mensageiro/metabolismo , Proteínas/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Dineínas/metabolismo , Movimento Celular/genética
2.
J Autism Dev Disord ; 53(2): 624-632, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33459916

RESUMO

Previous research has identified possible sex-based differences in restricted and repetitive behaviors in autism spectrum disorder (ASD). However, this finding is mixed, particularly among preschool-aged children. We investigated the presence of sex-based differences in parent-rated ASD symptomatology, using the Autism Spectrum Rating Scale (ASRS). Participants consisted of a large (n = 481,100 female), clinically-referred sample of preschoolers (ages 2-5) diagnosed with ASD (NVIQ: M = 67.11, SD = 21.79). Females had less severe symptoms on the Total, Unusual Behaviors, DSM-5, and Stereotypy scales on the ASRS. The effects were small-to-medium, but statistically significant. There was evidence of differential relationships between nonverbal IQ and ASRS scores among males and females. This study provides additional evidence of sex-based differences in ASD symptoms present from an early age.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno de Movimento Estereotipado , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Transtorno do Espectro Autista/diagnóstico , Comportamento Estereotipado , Pais
3.
J Autism Dev Disord ; 53(9): 3683-3699, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35831693

RESUMO

A randomized controlled trial established initial efficacy of a novel parent training (PT) intervention for improving oral hygiene and oral health in underserved children with ASD (Fenning et al., 2022), a population at risk for unmet dental needs. The present study describes our emic approach to PT development alongside treatment outcome data examining feasibility, acceptability, and engagement. Families with Medicaid-eligible children with ASD ages 3 to 13 years (85% male, 62% with intellectual disability) were assigned to receive PT (n = 60) or a psychoeducational toolkit (n = 59). Results indicate strong retention, fidelity, and adherence, with quantitative and qualitative metrics revealing high treatment satisfaction and utilization. Discussion focuses on implications for individualizing treatment to optimize engagement of underrepresented families.


Assuntos
Transtorno do Espectro Autista , Humanos , Criança , Masculino , Feminino , Transtorno do Espectro Autista/terapia , Pais/educação , Resultado do Tratamento , Comportamentos Relacionados com a Saúde
4.
J Autism Dev Disord ; 53(10): 3787-3798, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35879640

RESUMO

Behavior problems in children with autism spectrum disorder (ASD) may exacerbate parenting stress. Parenting self-efficacy and family resources may influence this association. We examined cross-sectional statistical mediation effects of parenting self-efficacy on the relationship between child behavior problems and parenting stress and hypothesized that family-level resources moderated this indirect effect. Participants included 132 underserved (Medicaid-eligible) children with ASD (ages 3-13) with racial/ethnic diversity; many (63%) had intellectual disability. Greater externalizing problems were linked with lower parenting self-efficacy, which in turn was associated with increased parenting stress. A larger mediation effect was observed for families with fewer resources. A plausible alternative model (parenting stress mediating parenting self-efficacy) exhibited poorer fit. Implications for family supports and benefits of longitudinal follow-up are discussed.


Assuntos
Transtorno do Espectro Autista , Comportamento Problema , Humanos , Criança , Poder Familiar , Autoeficácia , Estudos Transversais , Estresse Psicológico , Comportamento Infantil , Pais
5.
Sex Reprod Healthc ; 32: 100733, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35576736

RESUMO

Trans men and non-binary persons assigned female at birth (AFAB) often encounter resistance and reluctance pertaining to their healthcare needs. As a result of patriarchal-based decision-making and cis-heteronormative ideologies, the trans and gender diverse (TGD) population is routinely left out of representation in research, education, and healthcare. The aim of this integrative literature review is to describe the experiences of trans men and non-binary persons AFAB in healthcare interactions and their sexual and reproductive healthcare needs. A total of 32 articles were analyzed, synthesized, and reconceptualized through joint inductive and deductive analysis with a transfeminist and intersectional lens. From these papers, two broader concepts emerged with five sub-concepts that portrayed underlying barriers to care (primed with fear, onus of self-advocacy, and call for competence) and internalized ideologies (pregnancy incompatibility and presumptive care). A multidisciplinary approach is essential to employ in implementation efforts involving improved standards of care and in achieving desired family planning. As this is not as linear as addressing a knowledge gap, but one of deeper set intrinsic ideologies, instruction on the necessary impact of continued education and peer learning within the context of in-group dynamics can help the efficiency of designated change agents within the healthcare systems themselves.


Assuntos
Pessoas Transgênero , Atenção à Saúde , Serviços de Planejamento Familiar , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Educação Sexual , Comportamento Sexual
6.
Pediatrics ; 149(5)2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35211746

RESUMO

OBJECTIVE: Children with autism spectrum disorder (ASD) have difficulty participating in dental care and experience significant unmet dental needs. We examined the efficacy of parent training (PT) for improving oral hygiene and oral health in underserved children with ASD. METHOD: Families of Medicaid-eligible children with ASD (ages 3-13 years, 85% boys, 62% with intellectual disability) reporting difficulty with dental care participated in a 6-month randomized controlled trial comparing PT (n = 60) with a psychoeducational dental toolkit (n = 59). Primary outcomes were parent-reported frequency of twice-daily toothbrushing and dentist-rated visible plaque. Secondary outcomes included parent-reported child behavior problems during home oral hygiene and dentist-rated caries. Dentists were blind to intervention assignment. Analyses were intention to treat. RESULTS: Retention was high at posttreatment (3 months, 93%) and 6-month follow-up (90%). Compared with the toolkit intervention, PT was associated with increased twice-daily toothbrushing at 3 (78% vs 55%, respectively; P < .001) and 6 (78% vs 62%; P = .002) months and a reduction in plaque at 3 months (intervention effect, -0.19; 95% confidence interval [CI], -0.36 to -0.02; P = .03) and child problem behaviors at 3 (-0.90; 95% CI, -1.52 to -0.28; P = .005) and 6 (-0.77; 95% CI, -1.39 to -0.14; P = .02) months. Comparatively fewer caries developed in children receiving the PT intervention over 3 months (ratio of rate ratios, 0.73; 95% CI, 0.54 to 0.99; P = .04). CONCLUSIONS: PT represents a promising approach for improving oral hygiene and oral health in underserved children with ASD at risk for dental problems.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Cárie Dentária , Comportamento Problema , Adolescente , Transtorno do Espectro Autista/terapia , Criança , Pré-Escolar , Assistência Odontológica , Cárie Dentária/terapia , Feminino , Humanos , Masculino , Pais/educação
7.
J Autism Dev Disord ; 52(12): 5342-5355, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35013866

RESUMO

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1ß, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.


Assuntos
Transtorno do Espectro Autista , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Criança , Pré-Escolar , Humanos , Transtorno do Espectro Autista/tratamento farmacológico , Biomarcadores , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/uso terapêutico , Interleucina-2/metabolismo
8.
BMJ Glob Health ; 7(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983787

RESUMO

INTRODUCTION: Neonatal mortality rate (NMR) has been declining in sub-Saharan African (SSA) countries, where historically rural areas had higher NMR compared with urban. The 2015-2016 Demographic and Health Survey (DHS) in Tanzania showed an exacerbation of an existing pattern with significantly higher NMR in urban areas. The objective of this study is to understand this disparity in SSA countries and examine the specific factors potentially underlying this association in Tanzania. METHODS: We assessed urban-rural NMR disparities among 21 SSA countries with four or more DHS, at least one of which was before 2000, using the DHS StatCompiler. For Tanzania DHS 2015-2016, descriptive statistics were carried out disaggregated by urban and rural areas, followed by bivariate and multivariable logistic regression modelling the association between urban/rural residence and neonatal mortality, adjusting for other risk factors. RESULTS: Among 21 countries analysed, Tanzania was the only SSA country where urban NMR (38 per 1000 live births) was significantly higher than rural (20 per 1,000), with largest difference during first week of life. We analysed NMR on the 2015-2016 Tanzania DHS, including live births to 9736 women aged between 15 and 49 years. Several factors were significantly associated with higher NMR, including multiplicity of pregnancy, being the first child, higher maternal education, and male child sex. However, their inclusion did not attenuate the effect of urban-rural differences in NMR. In multivariable models, urban residence remained associated with double the odds of neonatal mortality compared with rural. CONCLUSION: There is an urgent need to understand the role of quality of facility-based care, including role of infections, and health-seeking behaviour in case of neonatal illness at home. However, additional factors might also be implicated and higher NMR within urban areas of Tanzania may signal a shift in the pattern of neonatal mortality across several other SSA countries.


Assuntos
Mortalidade Infantil , População Rural , Adolescente , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Parto , Gravidez , Tanzânia/epidemiologia , População Urbana , Adulto Jovem
9.
J Clin Child Adolesc Psychol ; 50(5): 669-681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33448884

RESUMO

Objective: Assessment of intellectual abilities in individuals with autism spectrum disorder (ASD) is a core component of a comprehensive diagnostic evaluation. However, relatively limited information is available regarding the validity of one of the most commonly-used measures of intelligence, the Wechsler Intelligence Scale for Children - 5th Edition (WISC-V) in ASD.Method: We investigated the factor structure and measurement invariance of the WISC-V in a sample of 349 children aged 6-16 diagnosed with ASD using single- and multi-group confirmatory factor analysis. The comparison group was the WISC-V standardization sample.Results: A four-index bifactor solution best fit the ASD group data. Measurement invariance analyses indicated support for configural and metric, but not scalar, invariance of the published 5-index structure, suggesting systematic differences in performance among some subscales in ASD. The 7-subtest FSIQ scale had partial scalar invariance after relaxing equality constraints on the Coding and Digit Span subtest intercepts, suggesting sources other than theorized IQ ability contribute to lower scores on these subtests within ASD. The Cognitive Proficiency Index (CPI) failed to demonstrate appropriate fit in baseline models. The General Ability Index (GAI) had full configural, metric, and scalar invariance.Conclusions: Statistical bias on the WISC-V within ASD in processing speed and working memory subtests creates significant limitations for the use of FSIQ and especially CPI index scores in ASD populations. The GAI showed strong measurement properties and should be considered as the preferred indicator of overall intellectual functioning when assessing children with ASD using the WISC-V.


Assuntos
Transtorno do Espectro Autista , Adolescente , Criança , Cognição , Análise Fatorial , Humanos , Memória de Curto Prazo , Escalas de Wechsler
10.
Autism Res ; 13(11): 1867-1879, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33001561

RESUMO

The Autism Impact Measure (AIM) was designed specifically for treatment-outcome assessment in children with ASD, focusing on treatment-relevant aspects of symptom presentation and efficient detection of short-term improvement. The AIM demonstrated strong reliability and validity in initial psychometric studies. The current study evaluated the AIM's sensitivity to change across well-established treatments. The sample included 471 children with ASD (ages 2-14) participating in one of six treatments. The AIM was administered at baseline and 6-week intervals and a battery of domain-specific concurrent measures was also administered. A longitudinal repeated measures design examined the degree to which: (a) AIM domain scores changed over time in response to treatment and (b) change in AIM domains was associated with change in measures of similar constructs. Results across growth curve models indicated that AIM domains are sensitive to change in symptoms across treatment. Across all models, symptoms decreased over time, with some deceleration in rate of improvement. For all AIM domains except Repetitive Behavior, symptoms improved as a function of treatment group. Correlations of change between AIM and other measures varied across domains (from 0.01-0.43 across measures). This was the first large-scale study to systematically evaluate sensitivity to change in a measure of core ASD symptoms. The results provide support for the AIM's ability to detect short-term improvement across symptom domains and indicate that AIM domains are sensitive to change overall and as a function of different treatment conditions. The brief repeated assessment window also highlights the AIM's utility for detecting improvements across short-term treatments. Autism Res 2020, 13: 1867-1879. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: Good measures are important for assessing outcomes in children with autism. However, there are few tools for tracking short-term changes in autism symptoms. This study tested a new measure, the Autism Impact Measure (AIM), in a large group of children with autism. The results showed that the AIM appears to be a valid and accurate tool for measuring autism symptoms. The AIM may be a helpful tool for researchers and clinicians interested in tracking short-term improvements in autism symptoms.


Assuntos
Transtorno Autístico , Adolescente , Criança , Pré-Escolar , Cognição , Humanos , Psicometria , Reprodutibilidade dos Testes
11.
J Child Adolesc Psychopharmacol ; 30(8): 512-521, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32746626

RESUMO

Objective: The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS. Methods: We assessed the ABC's factor structure (with both exploratory and confirmatory analyses) in 797 people with FXS and we compared these findings with exploratory factors derived from an independent sample of 357 individuals with FXS. In an ancillary analysis, we compared the overlap of the traditional ABC's Social Withdrawal scores with the Social Avoidance scores from the FXS-derived newer scale to determine whether overlap between these was very high and essentially redundant. Finally, we computed norms using both the traditional and the FXS-specific algorithms. Results: In confirmatory factor analyses, the FXS-specific algorithm produced the most consistent factor structure for the sample of 797 participants, but model fit was only marginally better than that derived by the original ABC scoring algorithm. Comparisons of factor structures from separate exploratory analyses revealed no consistent advantage of the FXS algorithm over the traditional algorithm. While a Social Avoidance subscale did emerge in some analyses, in other analyses, this was accompanied by loss of coherence on other domains of interest, such as the Socially Unresponsive/Social Withdrawal subscale. Conclusion: We question whether the newer FXS scoring algorithm contributes data that are consistently helpful in evaluating behavior of people with FXS. In general, we recommend continued use of the original ABC algorithm for scoring behavior of clients with FXS. However, we acknowledge that there may be circumscribed times when the new algorithm may be appropriate for scoring, namely when anxiety and/or social avoidance constructs are the central and unequivocal domains of interest.


Assuntos
Lista de Checagem/normas , Análise Fatorial , Síndrome do Cromossomo X Frágil/complicações , Comportamento Problema , Algoritmos , Ansiedade , Criança , Feminino , Humanos , Humor Irritável , Masculino , Transtornos Mentais/complicações , Ajustamento Social
12.
J Autism Dev Disord ; 50(7): 2307-2319, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29344761

RESUMO

The Autism Impact Measure (AIM) was designed to track incremental change in frequency and impact of core ASD symptoms. The current study examined the structural and convergent validity of the AIM in a large sample of children with ASD. The results of a series of exploratory and confirmatory factor analyses yielded a final model with five theoretically and empirically meaningful subdomains: Repetitive Behavior, Atypical Behavior, Communication, Social Reciprocity, and Peer Interaction. The final model showed very good fit both overall and for each of the five factors, indicating excellent structural validity. AIM subdomain scores were significantly correlated with measures of similar constructs across all five domains. The results provide further support for the psychometric properties of the AIM.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Testes Psicológicos/normas , Adolescente , Criança , Pré-Escolar , Cognição , Comunicação , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Comportamento Estereotipado , Inquéritos e Questionários
13.
Elife ; 62017 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-29117894

RESUMO

Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The 'specification model' postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the 'migration model' posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling.


Assuntos
Movimento Celular , Mesoderma/embriologia , Ligantes da Sinalização Nodal/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Proteínas de Peixe-Zebra/metabolismo , Animais , Técnicas de Inativação de Genes , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
14.
Genetics ; 205(2): 737-748, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27913619

RESUMO

During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to neurofibromatosis type II, characterized by benign tumors of glial tissues. Here we demonstrate that in C. elegans, nfm-1 is required for the ability of Q cells and their descendants to extend protrusions and to migrate, but is not required for direction of migration. Using a combination of mosaic analysis and cell-specific expression, we show that NFM-1 is required nonautonomously, possibly in muscles, to promote Q lineage migrations. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might be involved in the generation of an extracellular cue that promotes Q neuroblast protrusion and migration that acts with or in parallel to SLT-1 In vertebrates, NF2 and Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migratory events.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Movimento Celular , Proteínas do Tecido Nervoso/genética , Células-Tronco Neurais/metabolismo , Neurofibromina 1/genética , Animais , Orientação de Axônios , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Células-Tronco Neurais/fisiologia , Neurofibromina 1/metabolismo
15.
G3 (Bethesda) ; 5(8): 1567-74, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26022293

RESUMO

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Sindecana-1/metabolismo , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Movimento Celular , Proteínas de Membrana/genética , Neurônios/citologia , Sindecana-1/genética
16.
J Ment Health Res Intellect Disabil ; 7(4): 306-322, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25419257

RESUMO

Youth with autism spectrum disorder (ASD) often present with emotional problems such as anxiety and depression (American Psychiatric Association, 2013). A recent study of the Child Behavior Checklist 6-18 (CBCL; Achenbach & Rescorla, 2001) indicated good sensitivity but relatively low specificity for identifying emotional problems in youth with ASD. The current study examined the extent to which variance in the CBCL's Anxious/Depressed, Withdrawn/Depressed, Internalizing Domain, and Total Problems scales was accounted for by symptoms of emotional problems relative to ASD symptoms. Correlation and multiple regression analyses indicated that these scales measured anxiety and depression but a small statistically significant proportion of variance in Total Problems scores was also accounted for by ASD symptoms. Results contribute to the emerging evidence base for the inclusion of the CBCL in assessment protocols for assessing emotional and behavioral problems in youth with ASD.

17.
Dev Biol ; 392(2): 141-52, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24954154

RESUMO

Directed migration of neurons is critical in the normal and pathological development of the brain and central nervous system. In Caenorhabditis elegans, the bilateral Q neuroblasts, QR on the right and QL on the left, migrate anteriorly and posteriorly, respectively. Initial protrusion and migration of the Q neuroblasts is autonomously controlled by the transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21. As QL migrates posteriorly, it encounters and EGL-20/Wnt signal that induces MAB-5/Hox expression that drives QL descendant posterior migration. QR migrates anteriorly away from EGL-20/Wnt and does not activate MAB-5/Hox, resulting in anterior QR descendant migration. A forward genetic screen for new mutations affecting initial Q migrations identified alleles of cdh-4, which caused defects in both QL and QR directional migration similar to unc-40, ptp-3, and mig-21. Previous studies showed that in QL, PTP-3/LAR and MIG-21 act in a pathway in parallel to UNC-40/DCC to drive posterior QL migration. Here we show genetic evidence that CDH-4 acts in the PTP-3/MIG-21 pathway in parallel to UNC-40/DCC to direct posterior QL migration. In QR, the PTP-3/MIG-21 and UNC-40/DCC pathways mutually inhibit each other, allowing anterior QR migration. We report here that CDH-4 acts in both the PTP-3/MIG-21 and UNC-40/DCC pathways in mutual inhibition in QR, and that CDH-4 acts cell-non-autonomously. Interaction of CDH-4 with UNC-40/DCC in QR but not QL represents an inherent left-right asymmetry in the Q cells, the nature of which is not understood. We conclude that CDH-4 might act as a permissive signal for each Q neuroblast to respond differently to anterior-posterior guidance information based upon inherent left-right asymmetries in the Q neuroblasts.


Assuntos
Caderinas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Movimento Celular/fisiologia , Sistema Nervoso Central/embriologia , Células-Tronco Neurais/fisiologia , Transdução de Sinais/fisiologia , Animais , Caderinas/genética , Proteínas de Caenorhabditis elegans/genética , Moléculas de Adesão Celular/metabolismo , Componentes do Gene , Proteínas de Membrana/metabolismo , Microscopia Confocal , Células-Tronco Neurais/metabolismo , Proteínas Tirosina Fosfatases
18.
Mol Cell ; 54(6): 946-959, 2014 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-24910101

RESUMO

Alternative splicing is important for the development and function of the nervous system, but little is known about the differences in alternative splicing between distinct types of neurons. Furthermore, the factors that control cell-type-specific splicing and the physiological roles of these alternative isoforms are unclear. By monitoring alternative splicing at single-cell resolution in Caenorhabditis elegans, we demonstrate that splicing patterns in different neurons are often distinct and highly regulated. We identify two conserved RNA-binding proteins, UNC-75/CELF and EXC-7/Hu/ELAV, which regulate overlapping networks of splicing events in GABAergic and cholinergic neurons. We use the UNC-75 exon network to discover regulators of synaptic transmission and to identify unique roles for isoforms of UNC-64/Syntaxin, a protein required for synaptic vesicle fusion. Our results indicate that combinatorial regulation of alternative splicing in distinct neurons provides a mechanism to specialize metazoan nervous systems.


Assuntos
Processamento Alternativo/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/genética , Neurônios Colinérgicos/citologia , Neurônios GABAérgicos/citologia , Proteínas de Ligação a RNA/fisiologia , Transmissão Sináptica/genética , Sintaxina 1/genética , Animais , Neurônios Colinérgicos/metabolismo , Neurônios GABAérgicos/metabolismo , Mutação , Sistema Nervoso/embriologia , Sistema Nervoso/crescimento & desenvolvimento , Isoformas de Proteínas/genética , Proteínas de Ligação a RNA/genética , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/metabolismo
19.
Science ; 343(6172): 1248636, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24407481

RESUMO

It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.


Assuntos
Movimento Celular , Gastrulação/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Sequência de Aminoácidos , Animais , Receptores de Apelina , Quimiocina CXCL12/metabolismo , Mutação da Fase de Leitura , Gastrulação/genética , Dados de Sequência Molecular , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
20.
J Autism Dev Disord ; 42(9): 1949-58, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22274777

RESUMO

The Children's Interview for Psychiatric Syndromes-Parent Version (P-ChIPS) is a structured psychiatric interview designed to assess the presence of psychiatric disorders in children and adolescents. This study examined the reliability and validity of the P-ChIPS in 61 youngsters (6- to 17-years-old) with Autism Spectrum Disorders. Reliability analyses were conducted according to level of functioning and language level. Results indicated that interrater reliability values were largely in the good to excellent range. Concordance between the P-ChIPS and the Child and Adolescent Symptoms Inventory was fair for the majority of disorders. Percent overall agreement for most disorders was good, lending support to the validity of the P-ChIPS. The results of this study suggest that the P-ChIPS is appropriate for this population.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Entrevista Psicológica , Escalas de Graduação Psiquiátrica , Adolescente , Criança , Psiquiatria Infantil , Feminino , Humanos , Masculino , Pais , Psicometria , Reprodutibilidade dos Testes
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